TGF-beta-activated kinase 1 stimulates NF-kappa B activation by an NF-kappa B-inducing kinase-independent mechanism.
Several mitogen-activated protein kinase kinase kinases (MAPKKKs), including NF-kappa B-inducing kinase (NIK), play critical roles in NF-kappa B activation. We isolated cDNA for human TGF-beta activated kinase 1 (TAK1), a member of the MAPKKK family, and evaluated its ability to stimulate NF-kappa B activation. Overexpression of TAK1 together with its activator protein, TAK1 binding protein 1 (TAB1), induced the nuclear translocation of NF-kappa B p50/p65 heterodimer accompanied by the degradation of I kappa B alpha and I kappa B beta, and the expression of kappa B-dependent reporter gene. A dominant negative mutant of NIK did not inhibit TAK1-induced NF-kappa B activation. These results suggest that TAK1 induces NF-kappa B activation through a novel NIK-independent signaling pathway.
Sakurai
H
H
Lead Generation Research Laboratory, Tanabe Seiyaku Co., Ltd., Osaka, Japan.
Shigemori
N
N
Hasegawa
K
K
Sugita
T
T
D048868:Adaptor Proteins, Signal Transducing; D017398:Alternative Splicing / Q000235:genetics; D002352:Carrier Proteins / Q000378:metabolism; D003001:Cloning, Molecular; D005786:Gene Expression Regulation / Q000235:genetics; D006367:HeLa Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D020930:MAP Kinase Kinase Kinases; D016328:NF-kappa B / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry* / Q000235:genetics* / Q000502:physiology; D012333:RNA, Messenger / Q000032:analysis; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction / Q000502:physiology; D014162:Transfection / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D000097782:NF-kappaB-Inducing Kinase; D000099151:MAP Kinase Kinase Kinase 7
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; D020930:MAP Kinase Kinase Kinases; D016328:NF-kappa B; D017346:Protein Serine-Threonine Kinases; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D000097782:NF-kappaB-Inducing Kinase; D000099151:MAP Kinase Kinase Kinase 7; C099510:TAB1 protein, MAPKKK activator, vertebrate; C486300:TAB1 protein, human